Plasmodium vivax morbidity after radical cure: A cohort study in Central Vietnam

Abstract

Background In Vietnam, the importance of vivax malaria relative to falciparum during the past decade has steadily increased to 50%. This, together with the spread of multidrug-resistant Plasmodium falciparum , is a major challenge for malaria elimination. A 2-year prospective cohort study to assess P . vivax morbidity after radical cure treatment and related risk factors was conducted in Central Vietnam. Methods and findings The study was implemented between April 2009 and December 2011 in four neighboring villages in a remote forested area of Quang Nam province. P . vivax -infected patients were treated radically with chloroquine (CQ; 25 mg/kg over 3 days) and primaquine (PQ; 0.5 mg/kg/day for 10 days) and visited monthly (malaria symptoms and blood sampling) for up to 2 years. Time to first vivax recurrence was estimated by Kaplan–Meier survival analysis, and risk factors for first and recurrent infections were identified by Cox regression models. Among the 260 P . vivax patients (61% males [159/260]; age range 3–60) recruited, 240 completed the 10-day treatment, 223 entered the second month of follow-up, and 219 were followed for at least 12 months. Most individuals (76.78%, 171/223) had recurrent vivax infections identified by molecular methods (polymerase chain reaction [PCR]); in about half of them (55.61%, 124/223), infection was detected by microscopy, and 84 individuals (37.67%) had symptomatic recurrences. Median time to first recurrence by PCR was 118 days (IQR 59–208). The estimated probability of remaining free of recurrence by month 24 was 20.40% (95% CI [14.42; 27.13]) by PCR, 42.52% (95% CI [35.41; 49.44]) by microscopy, and 60.69% (95% CI [53.51; 67.11]) for symptomatic recurrences. The main risk factor for recurrence (first or recurrent) was prior P . falciparum infection. The main limitations of this study are the age of the results and the absence of a comparator arm, which does not allow estimating the proportion of vivax relapses among recurrent infections. Conclusion A substantial number of P . vivax recurrences, mainly submicroscopic (SM) and asymptomatic, were observed after high-dose PQ treatment (5.0 mg/kg). Prior P . falciparum infection was an important risk factor for all types of vivax recurrences. Malaria elimination efforts need to address this largely undetected P . vivax transmission by simultaneously tackling the reservoir of P . falciparum and P . vivax infections.

Plasmodium vivax in Children: Hidden Burden and Conspicuous Challenges, a Narrative Review

“…Among recurrent cases, it is not possible to distinguish between P. vivax reinfections (new inoculation of sporozoite), relapses (activation of latent hypnozoites), and recrudescence (the resurgence of erythrocytic parasites), because molecular markers have not yet been fully validated [ 81 – 83 ]. However, by analyzing seasonal patterns of malaria, it is possible to estimate the proportion of cases due to relapse versus reinfection [ 84 ].…”

Why using bed nets is a challenge among minority populations in Central Vietnam

“…Village 1, where the highest number of vivax malaria cases was reported in the main cohort study in 2009, was selected for the survey [ 24 ]. The sampling frame consisted of households registered in the 2009 census, who were all invited to answer the questionnaire.…”

“…This paper reports the results of a mixed-methods study assessing factors limiting the uptake of ITNs in an ethnic minority setting in a remote forested area of Central Vietnam. This study was embedded in a larger community-based cohort study on the epidemiology of Plasmodium vivax [ 23 , 24 ].…”

Why Using Bed Nets is a Challenge amongst Minority Populations in Central Vietnam

“…Sampling. Village 1 was selected for the survey as it had the highest number of vivax malaria cases in the main cohort study in 2009 [32]. The sampling frame consisted of households registered in the 2009 census, who were all invited to answer the questionnaire.…”

“…This paper reports the results of a mixed-method study assessing local factors limiting the uptake of bednets amongst ethnic minority groups living in a remote forested area of central Vietnam. This study was embedded in a larger community-based cohort study on the epidemiology of Plasmodium vivax [31,32].…”